Brief of - Low-dose exposure to malathion and radiation results in the dysregulation of multiple neuronal processes, inducing neurotoxicity and neurodegeneration in mouse

Document Type

Article

Abstract

Key Findings

  • Malathion and radiation exposure dysregulate neuronal processes and induce neurotoxicity.
  • Altered processes include synaptic transmission, neuronal survival, and proliferation.
  • Exposure to malathion and IR can lead to overlapping biological processes affecting neuronal functions.
  • Exposure to neurotoxicants at a young age can trigger neurodegenerative-like symptoms.

Objectives

  • The study aimed to investigate the effects of IR, malathion, and their combination on neuronal markers, dendritic morphology, antioxidant levels, and gene expression in the hippocampus.

Methods

  • C57BL/6 male mice were orally administered malathion and exposed to radiation.
  • Tissue processing, immunohistochemistry, enzyme assays, and mRNA isolation were performed.
  • Behavioral experiments were conducted to assess exploratory behavior, anxiety, memory, and recognition ability.
  • Transcriptomic studies were conducted to analyze changes on a genome-wide level and investigate alterations in cellular processes and signaling pathways post-exposure to IR, malathion, and their combination.
  • Protein-protein interaction (PPI) network analysis was conducted.

Results

  • IR and malathion exposure reduces neuronal maturity and dendritic spine density.
  • Antioxidant levels are decreased in the IR and co-exposure groups.
  • Differential gene expression analysis reveals numerous affected biological processes and pathways.
  • Alterations in major pathways such as MAPK, PI3K-Akt, apelin, NF-κB, and Notch signaling pathways were observed in the IR group.
  • Malathion exposure affected pathways related to AD, PD, Huntington’s disease, and ALS.
  • IR exposure resulted in changes in processes controlling neuronal functioning and neurotransmitter processes.
  • Co-exposure down regulated pathways related to neuronal functioning.
  • Exposure to neurotoxicants at a young age could lead to early neurodegenerative complications.
  • Molecular alterations did not immediately translate into functional changes in behavior.

Conclusions

  • Exposure to IR, malathion, and their combination induces neuroinflammation, impairs neuronal integrity, and alters gene expression in the hippocampus.
  • Exposure to malathion and IR can impact neuronal pathways and processes, potentially contributing to the development of neurodegenerative disorders.

Recommended Citation

Narasimhamurthy RK, Venkidesh BS, Nayak S, Reghunathan D, Mallya S, Sharan K, Rao BSS, Mumbrekar KD. Low-dose exposure to malathion and radiation results in the dysregulation of multiple neuronal processes, inducing neurotoxicity and neurodegeneration in mouse. Environmental science and pollution research international, 31, 1403–1418 (2024). https://doi.org/10.1007/s11356-023-31085-4

Publication Date

2024

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